Analyzer

ABSTRACT

An analyzer which comprises a conveyer which conveys sample cups and reaction cups intermixedly on a closed track, a reactor which maintains reaction cups at a predetermined temperature, a trashbin which collects used reaction cups, a nozzle unit, a reaction cup lift which carries a reaction cup between the conveyer, the reactor and the trashbin and a drive unit which drives the nozzle unit and the reaction cup lift to reciprocate, wherein the trashbin is placed on the straight track of the reaction cup lift, at least part of the closed track of the conveyer is straight and overlaps the straight track of the nozzle unit and the reaction cup lift, and the straight part of the track of the conveyer accommodates at least two cups.  
     An automatic analyzer which comprises a storage means which stores test order information, a first identification means which reads sample identification information, a work list preparing means which prepares a work list on the basis of the sample identification information, a loading order determination means which determines the order in which sample cups and reaction cups are loaded from the work list, a second identification means which automatically reads specific component information and a collating means which compares the specific component information with the work list.

[0001] The present invention relates to an analyzer for trace componentanalysis of samples such as blood, serum, plasma or urine, especially anautomatic analyzer for biochemical or immunological trace componentanalysis of such samples.

[0002] In the field of clinical diagnostics, analyzers are used widelyfor detection and determination of specific components in blood, serum,plasma or urea samples from examinees to provide useful data fordiagnoses of diseases. Among analyzers, multichannel biochemicalanalyzers determine saccharides, lipids and proteins by using enzymaticreactions and chemical reactions, and multichannel immunologicalanalyzers determine hormones and tumor markers by using specificinteraction between antigens and antibodies. These analyzers usuallyperform biochemical reactions and immunological reactions in individualdisposable reaction cups to avoid contamination among samples orreaction liquids. Prefilled reaction cups already containing a reagentfor a specific component in samples to be measured are usuallydisposable too.

[0003] Instrumental analyses as mentioned above usually cover more thanone specific component in a sample to make good use of samples fromexaminees or to secure more accurate diagnosis based on multiplecomponents.

[0004] To speed up and facilitate numerous operations necessary fordetermination of multiple specific components in samples, automaticanalyzers have been used routinely. Typical automatic analyzers inpresent use add given amounts of samples to prefilled reaction cupsalready containing reagents for measurement of specific components and,optionally, incubate and wash the reaction cups for determination ofvarious specific components in each sample.

[0005] Further, a full-automatic biochemical analyzer equipped with anautomatic loader which selects a prefilled reaction cup containing areagent proper for a specific component and places it on a tray on aconveyer (JP-B-3-58666) and an automatic analyzer with a conveyer whichautomates operations from conveyance of a sample cup to output of theresults once the operator places the sample cup and the reaction cup(JP-A-3-51762) are known.

[0006] Analyzers like these usually sucks a given amount of a samplefrom a sample cup into a reaction cup while conveying the sample cup andthe reaction cup on two separate conveyers to set off the reaction fordetermination of a specific component in the sample. However, thestructural complexity of an analyzer having two conveyers due to movableparts indispensable to the conveyers makes its maintenance difficult andleads to increase in its production cost and size. Therefore, conveyanceof a sample cup and a reaction cup by one conveyer has been suggested.

[0007] In biochemical and immunological analyses, it is common todetermine more than one specific component in a sample to make good useof samples from examinees and to secure more accurate diagnosis based onmultiple components. For such multiple analyses by an analyzer in whichsample cups and reaction cups share the same conveyers a sample cupcontaining a sample placed at an arbitrary position on the conveyer isfollowed by as many reaction cups as the measurements to be done withthe sample, namely the specific components to be measured in the sampleso that the sample and the reaction cups to be used for the analysis ofthe sample are conveyed successively. If it is necessary to dilute ortreat the sample beforehand, a diluent cup or the like is interposedbetween the sample and the reaction cups behind the sample.

[0008] An analyzer sucks a given amount of a sample from a sample cupinto a reaction cup on a moving conveyer, if necessary after preliminarydilution or pretreatment of the sample with a reagent, and if necessaryadds other reagents, to set off the reaction for determination of aspecific component in the sample. Because the sample cup and thereaction cups move on a single track on the same conveyer, the conveyerhas to position reaction cups just under the nozzle by making quickmotions immediately after a sample is sucked from the sample cupcontaining it at the same position so that the sample sucked from thesample cup is ejected into the reaction cups behind the sample cup.Therefore, the conveyer has to make quicker motions more frequently toincrease the through put speed.

[0009] If the motions of the conveyer get quicker and frequent, it isvirtually impossible to load additional sample cups or reaction cups onthe conveyer while the analyzer is in action, and the conveyer has to bescaled up to accommodate a lot of cups, sacrificing the advantageeasiness of downsizing and simplification of such an analyzer. Inaddition, it is quite difficult to conduct so-called “cut-in” analysesof samples in need of urgent analyses.

[0010] The first object of the present invention is to provide ananalyzer available in a small size and with simple structure by using asingle conveyer which conveys both sample cups and reaction cupsintermixedly at a moderate speed which allows loading of additionalsample cups or reaction cups on the conveyer in action

[0011] As described above, an automatic analyzer with a single conveyingmeans such as a conveyer is obtainable in a small size and with lightweight and reduced costs, while it is not free from the possibilitiesthat the operator loads sample cups or reaction cups in the wrong placesor the wrong reaction cups unsuited to the specific components to bemeasured by mistake.

[0012] Thus, misplacement of sample cups or reaction cups on theconveying means can make it impossible to conduct intended analyses evenwithout causing trouble in the subsequent automatic analyses and can endup with the wrong results because a reaction cup for a specificcomponent is used for a different specific component.

[0013] Accordingly, the second object of the present invention is toprovide an automatic analyzer which eliminates operational mistakes suchas misplacement of sample cups or reaction cups on a conveyer by anoperator as mentioned above and even detects, if happen, suchoperational mistakes.

[0014] To attain the above-mentioned first object of the presentinvention, the present invention provides an analyzer which determines aspecific component in a sample while conveying a sample cup containingthe sample and a reaction cup containing a reagent which reacts with thesample, which is characterized in that: (1) the analyzer comprises aconveyer which conveys sample cups and reaction cups intermixedly on aclosed track, (2) the analyzer comprises a reactor which is equippedwith a thermostat which maintains the reaction cups at a predeterminedtemperature, a trashbin which collects used reaction cups, an up-downnozzle unit which sucks in and out a predetermined amount of a sampleand a reaction cup lift which carries a reaction cup between theconveyer, the reactor and the trashbin, (3) the nozzle unit and thereaction cup lift reciprocate on a straight track, driven by differentdrive units separately or by the same drive unit, (4) the trashbin isplaced on the straight track of the reaction cup lift, (5) at least partof the closed track of the conveyer is straight and overlaps thestraight track of the nozzle unit and the reaction cup lift, and (6) thestraight part of the track of the conveyer accommodates at least twocups.

[0015] To attain the above-mentioned second object of the presentinvention, the present invention provides an automatic analyzer whichdetermines a specific component in a sample while intermixedly conveyinga sample cup containing the sample which present sample identificationinformation which identifies the sample in the sample cup and a reactioncup containing a reagent for determination of the specific component inthe sample which presents specific component information whichidentifies the specific component by one conveyer, wherein the automaticanalyzer comprises; (1) a storage means which stores test orderinformation including specific component information to identify atleast one specific component to be measured for each sample, (2) a firstidentification means which reads the sample identification informationpresented by each sample cup, (3) a work list preparing means whichselects the specific component information which identifies at least onespecific component in the sample to be measured from the test orderinformation stored in the storage means on the basis of the sampleidentification information for the sample read by the firstidentification means and prepares a work list consisting of the sampleidentification information for sample and the specific componentinformation identifying the specific component(s) in the sample to bemeasured, (4) a loading order determination means which determines theorder in which sample cups and reaction cups are loaded on the singleconveyer from the work list, (5) a second identification means whichautomatically reads the specific component information presented by areaction cup conveyed by the conveyer, and (6) a collating means whichcompares the specific component information read by the secondidentification means with the determined order and indicates whether ornot they are matched

[0016]FIG. 1 illustrates one embodiment of the analyzer of the presentinvention.

[0017]FIG. 2 is a sectional view of the analyzer shown in FIG. 1 (alongthe reciprocation tracks of the nozzle unit 2 and the reaction cup lift3).

[0018]FIG. 3 schematically outlines application of the present inventionto an automatic immunological analyzer.

[0019]FIG. 4 outlines a reaction cup.

[0020] The preset invention is applicable to an automatic analyzer whichdetermines specific components by using a different reagent for each orsome specific components at least partly prepacked in reaction cups.Such automatic analyzers include, for example, automatics immunologicalanalyzers which determine specific components in samples by usingimmunological reactions and automatic biochemical analyzers whichdetermine specific components in samples by using biochemical reactions.Now an automatic immunological analyzer embodying the present inventionwill be described in detail by reference to drawings.

[0021]FIG. 1 and FIG. 2 are top and sectional views of the analyzeraccording to the first aspect of the present invention.

[0022] A sample cup 10 contains a sample in it. As the sample, blood,serum, plasma and urine are used for immunological and biochemicalanalyzers, and river water and liquid extract from soil may be used assample for chemical analyzers for environmental analyses. Reaction cupsare used to provide space in which reactions of samples and reagentsnecessary for sample analyses are carried out, and may be empty orprefilled with reagents for determination of components to be measured(hereinafter referred to as “specific components”), depending on themode of the analysis. For example, biochemical analyzers mix a samplewith a chemical reagent which undergoes color-producing biochemicalreaction with a specific component in a reaction cup, whileimmunological analyzers mix a sample with an antigen or an antibodywhich undergoes an immunological reaction with a specific component in areaction cup. For analyses of samples which contain a specific componentat too high concentrations to measure or need certain pretreatment,dilution cups or pretreatment cups may be used to dilute samples or mixsamples with pretreatment reagents in them.

[0023] In cases of reaction cups prefilled with a reagent, the reagentmay be in a liquid state or a lyophilized state. When reaction cupscontain all the reagents necessary for analysis or when empty reactioncups are used, the reagents may be added into reaction cups beingconveyed by a conveyer or in the reactor which will be described later.Especially, for immunological analyzers, reaction cups prefilled withsuch a reagent as mentioned above are available. For example, indetermination of a specific substance by heterogeneous one step sandwichEIA, an antibody with binding specificity for the specific substanceimmobilized on water insoluble magnetic beads and another enzyme-labeledantibody with binding specificity for the specific substance may beprepacked after lyophilization. Reaction cups of this type are availablefor competitive EIA and assay using a fluorescent or chemiluminescentsubstance as a label instead of an enzyme as well as sandwich EIA.

[0024] The sample cups and reaction cups as above mentioned are loadedon a single conveyer 1 and conveyed on a closed track. The conveyer maybe comprised of, for example, an endless track of a conveyer belt or asnake belt, a drive unit such as a sprocket wheel 18 and a support forthe endless track, as shown in FIG. 1. In FIG. 1, the sprocket wheel 18also serves as the support. The sizes and shapes of sample cups andreaction cups and, if any, dilution and pretreatment cups may be thesame or different. When their sizes and is shapes are different, anadaptor may be used to fit them on the conveyer.

[0025] The conveyer 1 conveys sample cups and reaction cups intermixedlyon a closed track. The conveyer is preferred to be designed so thatevery two neighboring cups on the conveyer keep a constant intervalbetween their centers for the reason described later. The automaticanalyzer of the preset invention can be reduced in size as compared withanalyzers in which these different types of cups are conveyed by theirown conveyers. The conveyer is preferably driven intermittently so as tomove the same distance as the intervals of the centers of twoneighboring cups on it. As shown FIG. 1, a sample cup 10 is followed (orpreceded) by a reaction cup 12 containing a reagent proper for aspecific component in the sample in the sample cup 10, if present,across a dilution cup 11. Thus, in the analyzer of the presentinvention, two sample cups are not loaded on the conveyer, not intandem, so as to interpose at least one reaction cup between them. Notall samples require one dilution cup each, and some samples with no needfor dilution require no dilution cups, while samples which need at leasttwo steps of dilution require at least two dilution cups. The sameapplies to pretreatment cups.

[0026] A sample sucked from a sample cup and a reagent, if not prepackedin the reaction cup, are ejected into a reaction cup on the movingconveyer 1, optionally mixed with a solubilizer or other reagents, toset off the intended reaction. Subsequent washing (B/F separation step)by an appropriate method and addition of supplementary reagents arefollowed by detection of a signal indicating the presence orconcentration of the specific substance such as color, fluorescence orluminescence after a certain period of time, and the presence orconcentration of the specific substance is determined from the detectedsignal intensity.

[0027] The analyzer of the present invention transports a reaction cupfrom the conveyer 1 to the reactor 6 in the course of an analysis, toallow the reaction to proceed and detects the signal there. For thispurpose, the reactor 6 is furnished with a means for supporting reactioncups described later and various equipments. The reactor is equippedwith a thermostat which maintains reaction cups at a predeterminedtemperature at the least and maintains the temperature so that theintended reaction proceeds effectively in reaction cups transferredthereinto. The thermostat may be constructed, for example, by acombination of a temperature sensor and a heat source. The reactor 6 ispreferably designed so as to eliminate factors detrimental to sensitivedetection by the detector 8. For example, when the detector is aphotometric detector which detects fluorescence or luminescence, thereactor is preferably covered with a shade 14 entirely except for theopening 16 because scattering incident light from the outside canadversely affect the detection sensitivity. The shade over the reactor 6also has an effect of making the inside temperature of the reactor lesssusceptible to the outside temperature in addition to the shadingeffect.

[0028] The reactor 6 may be a rotational disk or a caterpillar similarto the conveyer 1 in itself, but preferably a disk with a view tosimplifying and downsizing the analyzer because a disc would be able toeasily bring any reaction cup right under the opening 16 by rotating ineither direction so that an arbitrary reaction cup could be inserted orwithdrawn through the opening. The discoid reactor 6 in FIG. 1 hashollow cup holders arranged on three concentric circles so that after asample and a proper reagent are ejected into a reaction cup, thereaction cup is placed in a hollow cup holder on the innermost or midcircle for a predetermined period, then transferred onto the outermostcircle by a reaction cup lift 26 and subjected to washing by a washer 7and detection by a detector 8 there.

[0029] The reactor 6 may be equipped variously depending on the analyzerto which the present invention is applied. For example, in the case ofan analyzer for enzyme-labeled heterogeneous immunoassay as describedabove, around the reactor 6, a magnet shaker (omitted in Figures) whichstirs the content of a reaction cup by movement of water insolublemagnetic beads prepacked in the reaction cup, a washer 7 (called a B/Fseparator) for separation of the labeled antibody not bound to themagnetic beads after the immunological reaction, a dispenser 9 whichadds the substrate of the labeling enzyme into a reaction cup and adetector 8 which detects fluorescence, absorbance or luminescence forassay of the activity of the labeling enzyme and the like may bearranged operatively.

[0030] Especially, the washer 7 is used for separation of the fractionbound to the water insoluble magnetic beads and the free fraction in theliquid phase and exemplarily has a double pipe structure composed of awashing liquid pipe connected to a washing liquid pressure pomp and aliquid evacuation pipe connected to a vacuum pump via a liquid trap soas to not only eject the wash liquid into a reaction cup but alsoevacuate the liquid only, leaving the solid phase. Because the waterinsoluble beads may be beads with diameters from about 1 to 10 nm orfine particles with diameters of submicron to several microns, it ispreferred to select the washer structure appropriately according to theshape and size of the beads. Magnetic beads as the water insolublecarrier can be cornered by a magnet in a reaction cup while the washingliquid is sucked out.

[0031] In particular, the detector 8 should be selected appropriatelyaccording to the signal to be detected. Specifically speaking, fordetection of color, fluorescence or luminescence, an absorptiometer, afluorometer or an emission spectrometer should be selected,respectively. Detection may be done preferably with a reaction solutionin a reaction cup in view of simplification and miniaturization of theanalyzer, though it may be done with a reaction solution in a detectioncuvette. For such a manner of detection, the detector may be so designedas to emit excitation light downward toward a reaction solution anddetect the signal from the reaction solution above it (on condition thatthere is an opening in the shade has). The methodology of detection isclassified according to the number of measurements as the one-pointdetection, the two-point detection based on the difference between twomeasured values obtained around a given time and the multi-pointdetection based on the rate of change in the measurement with timeobtained from measured values at at least three points of time, and isselected appropriately in view of the mechanism of generation of thesignal to be detected, For example, when alkaline phosphatase is used asthe label in combination of 4-methylumbelliferyl phosphate as thesubstrate, since 4-methylumbelliferyl phosphate gives off fluorescenceupon dephosphorylation by alkaline phosphatase, the fluorescentintensity is measured at a certain time after addition of the substratein solution by a fluorometric equipment.

[0032] The embodiment shown in FIG. 1 is provided with a dispenser 9exclusively used for the substrate, though the substrate may bedispensed into each reaction cup by means of the nozzle, because thesubstrate is added after the immunological reaction and does notparticipate in the immunological reaction, and such an exclusiveequipment can advantageously dispense the substrate into every cup inshorter time in the end.

[0033] In ordinary analyses, disposal reaction cups are usually used forthe above-mentioned reasons. The analyzer of the present inventioncarries a reaction cup after an analysis is completed by the detectionstep from the reactor 6 and dumped in the trashbin 17. For this purpose,the reaction lift is designed to move up and down. The reaction cup liftis used not only when a reaction cup is dumped, but also when a reactioncup is transferred from the conveyer 1 onto the reactor 6 after ejectionof a sample and a reagent into it. Holding of a reaction cup may besecured, for example, by providing a hang holder with three claws to thelift with while providing a groove or a flange to be bitten by the clawsaround the opening of the reactor.

[0034] The reaction cup lift is so designed to reciprocate on a straighttrack connecting the conveyer 1, the reactor 6 and the trashbin 17.Therefore, the closed track of the conveyer 1 should be straight atleast partly, and the reaction cup lift should be able to reciprocate ona straight track at least partially overlap the straight track. Thereaction cup lift may be lift up and down, for example, by fixing anozzle to an appropriate pedestal which is driven up and down by a motorvia a tangent screw. A motor and a tangent screw may also be used forthe reciprocation of the reaction cup lift on the straight track.Because the reaction cup lift 26 picks up or drops off a reaction cupwhere the reactor 6 crosses the straight track which the reaction cuplift follows to carry it from or to the reactor 6, when the reactor 6 iscovered with a shade 14 as mentioned above, the opening 16 of thereactor should be located on the straight track. In a particularlypreferable embodiment, part or all of the diameter of the discoidreactor 6 and the opening 16 are arranged on the straight track.

[0035] The analyzer of the present invention has an up-down nozzle unitwhich sucks or ejects a given amount of liquid to suck a sample out of asample cup into a reaction cup or suck a reagent out of a reagentreservoir into a reaction cup. The nozzle unit may consist of a nozzleand a syringe pump, and the nozzle unit is lifted up and down, forexample, by employing such a structure that a nozzle is fixed to anappropriate pedestal which is driven up and down by a motor via atangent screw.

[0036] In the analyzer of the present invention, the nozzle unit is sodesigned as to reciprocate on a track overlapping the straight part ofthe closed track of the conveyer. When the nozzle unit in the analyzerof the present invention sucks in a sample or the like with a disposaltip at the end to prevent contamination of samples or reagents, thestraight track of the nozzle unit preferably extends to a trashbin inwhich used tips are dumped. When ejection of a reagent into a reactioncup on the reactor 6 is essential to start the reaction, the straighttrack of the nozzle unit should extend to the reactor 6. Therefore, in apreferable embodiment, the nozzle unit and the reaction cup lift followsame the straight track.

[0037] The nozzle unit and the reaction cup lift may be driven by thesame drive unit as shown in FIG. 2 because they reciprocate on the samestraight track or overlapping straight tracks, though they may be drivenby different drive units.

[0038] In the analyzer of the present invention, at least part of theclosed track of the conveyer 1 should be straight. For example, thetrack may be shaped like a rectangle of which one side corresponds tothe straight part. Alternatively, the track may be shaped like a ellipseor a circle part of which is straight The straight part of the closedtrack of the conveyer should be adjusted to be long enough toaccommodate at least two cups. The embodiment shown in FIG. 1 canaccommodate six cups on the straight part in total.

[0039] The reason why the conveyer should accommodate at least two cupson the straight part is because when a least one specific substance insamples is determined, each sample requires one sample cup and at leastone reaction cup. When more than one specific substance in samples hasto be determined, the conveyer is preferably so designed to accommodateas many cups as the specific substances to be determined on the straightpart. However, if too many specific substances are to be determined, thenumber of cups is preferably controlled to ten at the maximum by thedrive unit for the conveyer so that the analyzer does not becomesizable. In the present invention, the conveyer is preferably designedso as to accommodate at least three cups on the straight part in view ofadditional operations such as dilution and pretreatment.

[0040] When the conveyer can accommodate a sample cup and all reactioncups required for the analysis of the sample in the sample cup on thestraight part of the closed track, the conveyer is stopped when all thecups are brought on the straight part of the closed track of theconveyer, and the nozzle unit is lifted up and down over the sample cupto suck in the sample, then driven to over the reaction cups by thenozzle unit drive and lifted up and down there to eject the sample intothe reaction cups. On the other hand, when the conveyer can notaccommodate all these cups on the straight part of the closed track, thesuction of the sample from the sample cup and the transfer of thereaction cups to just below the nozzle by the conveyer without movingthe nozzle unit are repeated as many times as required, or after apredetermined number of repetitions of the suction and the transfer, thenozzle unit is moved instead of the conveyer so as to eject the reminderin the nozzle. When ejection of a sample into reaction cups entailscontrolled movements of the conveyer like the latter case, the conveyerpreferably moves the same distance as the intervals of the centers oftwo neighboring cups on it at a time intermittently.

[0041] As described above, when all the reagents required for thereaction are not contained in prefilled reaction cups, the reagentswhich are lacking have to be ejected into the reaction cupsadditionally. When the analyzer of the present invention requires suchan operation, the prefilled reaction cups 13 are located on the straighttrack on which the nozzle unit reciprocates when more than one reagenthas to be added to the reaction cups, a reagent conveyer may be providedso as to convey the reservoirs for these reagents on a straight track 19which crosses the straight track for reciprocation of the nozzle unit,preferably at right angles. When the nozzle sucks or ejects the sampleor the like with a disposal tip, a tip rack 5 for these tips 4 is placedon the straight track 19 on which the nozzle unit reciprocates. When tipconsumption is large, a tip conveyer which supplies new tips mayexemplarily be provided so as to move across the straight reciprocationtrack of the nozzle unit, preferably at right angles, on the straighttrack 19. In the embodiment shown in FIG. 1, the reagent reservoir 13and the tip rack 5 are carried by the same conveyer on the straighttrack in one combination. The tip rack may be a commercially availableone that stocks 96 tips at the maximum in a lattice pattern.

[0042] Now, the functions of various parts of a immunological analyzerwhich adopts the present invention will be described. The analyzer usesprefilled reaction cups containing all the reagents necessary for theimmunological reaction of a specific substance like those describedabove.

[0043] If dilution of the sample 10′ is necessary, the sample and thedilution liquid 13 supplied as a reagent are dispensed by the nozzleunit in a calculated dilution ratio into a dilution cup 11′ locatedbehind the sample cup and homogenized. Homogenization is preferably doneby sucking the liquid mixture in the dilution cup in and out with thenozzle unit repeatedly in view of simplification of the analyzer, thoughmay be done by providing a vibrator which mechanically vibrates a cup onthe conveyer under the conveyer. After homogenization, the nozzle unitsucks a certain amount of the diluted is sample and ejects it intoreaction cups 12-1′ and 12-2′.

[0044] Reaction cups containing the appropriately diluted sample aretransferred from the conveyer 1 into the reactor 6 maintained at acertain temperature by the reaction cup lift 26. After a certain time ofreaction, they are transferred by rotation of the reactor 6 to thewasher 7 where the intact fraction which is not bound to the solid phaseis removed. After the washing, the reactor 6 rotates to bring thereaction cups to the substrate dispenser which adds the substrate whichgenerates a signal detectable by the detector 8 catalyzed by thelabeling enzyme and then rotates again to bring them to the detector 8which detects the signal. After the detection, the reaction cups arecarried by the reaction cup lift and dumped in the trashbin 17. Theresults of the detection by the detection 8 are put out to a calculator,which is omitted in the Figures.

[0045] Some samples need pretreatment before they are subjected to thegiven reaction. Such a case can be dealt with by controlling theanalyzer as in the above-mentioned case of dilution of samples, unlessthere is a long time lag after sample and a pretreatment reagent aremixed. If a long time lag is needed after the mixing, the conveyer hasto be stopped for a long time, and it is not impossible to run ananalysis in a short time. Therefore, in the analyzer of the presentinvention, the sample 10 and the pretreatment liquid 13 supplied as areagent are dispensed by the nozzle unit into a pretreatment cup 11′placed behind the sample cup, then the pretreatment cup is carried 6together with reaction cups by the reaction cup lift 26 to the reactorwhere the pretreatment reaction takes place. After the pretreatmentreaction, the pretreatment cup and the reaction cups are carried to atemporary station 15 on the reciprocation track of the reaction cup lift26 by the reaction cup lift 26, and the pretreated sample is sucked fromthe pretreatment cup into the reaction cups by the nozzle unit there.The reaction cups containing the pretreated sample sucked out arecarried to the reactor again by the reaction cup lift 26 and treated inthe same manner as described above. The temporary station shouldaccommodate at least two cups so that the pretreatment cup and areaction cup can stay there temporality. The temporary station isprovided on the track of the reaction cup lift 3 and may be provided inthe reactor 6. The pretreated sample may be dispensed into reaction cupsby bringing the respective cups to be handled under the nozzle after thepretreatment reaction in the reactor.

[0046]FIG. 3 outlines one embodiment of the automatic analyzer accordingto the second aspect of the present invention. 1 denotes information onan analysis order, 2 denotes a storage means, 3 denotes a sample cup, 4denotes a sample code, 5 denotes a first identification means, 6 denotesa work list preparing means, 7 denotes a display, 8 denotes a secondidentification means, 9 denotes a third identification means, 10 denotesa common conveyer, 11 denotes a reactor and detector, 12 denotes acollating means, and 13 denotes an output device which puts out theresults of the analysis. FIG. 4 illustrates a reaction cup.

[0047] A sample cup 3 is used to put a sample such as blood, serum,plasma or urine in and carries a sample code on the outer surface suchas the lateral surface which enables the first identification means toidentify the sample in it. Each sample code has to identify one sampleand may consist of English letters, numerals or combination thereof ormeaningless patterns but should be assigned individually. Preferableexamples of the sample cup in the present invention are a bloodcollection tube with a sticker carrying a bar code indicating Englishletters or numerals or such a meaningless pattern as mentioned above inprint on the lateral surface or a sample cup carrying a magneticrecording medium on the surface. In the present invention, the samplecode is preferred to be visibly identifiable like the above-mentionedcode and the like.

[0048] The reaction cup is prefilled with reagents necessary fordetermination of a specific component to be measured, as shown in FIG.4. As such reagents, chemical reagents which colors by biochemicallyreacting with the specific component may be mentioned for automaticbiochemical analyzers, and antibodies (antigens) which immunologicallyreact with the specific component and enzymes may be mentioned forautomatic immunological analyzers.

[0049] In the reaction cup shown in FIG. 4, the reagents forheterogeneous one-step sandwich EIA of ferritin, a protein found inblood or serum samples, are contained. Specifically speaking, thecontent of the reaction cup is a lyophilized mixture of an antibody withFER-binding specificity immobilized on water insoluble magnetic beadsand another antibody with FER-binding specificity labeled with anenzyme. Reaction cups with such a structure are useful for competitiveEIA and immunoassay using a fluorescent or chemiluminescent substance asthe label instead of an enzyme in addition to sandwich EIA.

[0050] The reagents in a reaction cup may be in a liquid state or alyophilized state, as mentioned above for FIG. 4. It is possible to putin each sample cup reagents exclusive to the specific component to bemeasured in the reaction cup beforehand and then add reagents common toall the specific components while the reaction cups are conveyed by aconveyer.

[0051] A reaction cup not only keeps the above-mentioned reagents in itbut also provides space for reaction of the sample with the reagents,and carries specific component information on the lateral surface or onthe tacky foil covering the open top as shown in FIG. 4. Each componentcode should identify the specific component with which the reagents inthe reaction cup is used to react, and may consist of English letters,numerals or combination thereof or meaningless patterns. Preferableexamples of the reaction cup in the present invention are a plastic cupwith a sticker carrying a bar code indicating English letters ornumerals or such a meaningless pattern as mentioned above in print onthe lateral surface or a cup carrying a magnetic recording medium on thesurface. The reaction cup shown in FIG. 4 containing reagents for FERdetermination, carries a dot code indicating “FER” together with theletters “FER” and its lot number on the tacky foil covering the open topso that they are visibly identifiably by an operator.

[0052] The component information on the reaction cup not only indicateswhich specific component the reaction cup s is used for but alsospecifies measurement parameters necessary for determination of thecomponent such as the volume of the sample to be used for thedetermination, the volume of the dilution liquid to be added to thesample, the kinds and amounts of reagents to be added in addition to thereagents prepacked in the reaction cup, the calibration curve to be usedat the final stage.

[0053] The sample cup and reaction cup as described above are placed ona common conveyer 10 and then carried. The conveyer which carries themmay be comprised of, for example, an endless track of a conveyer belt ora snake belt, a drive unit such as a sprocket wheel 18 and a support forthe endless track.

[0054] The conveyer 10 sample cups and reaction cups intermixedly.Therefore, the automatic analyzer of the preset invention can be reducedin size as compared with those having a different conveyer for each typeof cups.

[0055] In the embodiment shown in FIG. 3, a sample cup A is preceded bya reaction cup B containing a reagent for measurement of a specificcomponent in the sample in the sample cup A, and further by a sample cupC and reaction cups D and F containing reagents for measurements ofspecific components in the sample in the sample cup C. Thus, theanalyzer of the present invention places two sample cups on theconveyer, not in tandem, so as to interpose at least one reaction cupbetween them.

[0056] The automatic analyzer of the present invention is furnished withvarious equipments 11 which encourages the reaction utilized fordetermination of a specific component such as a biochemical reaction ora immunological reaction or measures the reaction product as the signalof the presence of the specific component. Such equipments may beprovided appropriately depending on the type of assay the automaticanalyzer of the present invention uses. For example, an automaticimmunological analyzer for enzyme-labeled heterogeneous immunoassay maybe furnished with an incubator which maintains reaction cups at a giventemperature, a pipette which sucks a given amount of samples from samplecups into reaction cups, a magnet shaker which stirs the content of areaction cup by movement of water insoluble magnetic beads prepacked inthe reaction cup, a washer (called a B/F separator) for separation ofthe labeled antibody not bound to the magnetic beads after theimmunological reaction, a dispenser which adds the substrate of thelabeling enzyme into a reaction cup, a detector which detectsfluorescence, absorbance or luminescence for assay of the activity ofthe labeling enzyme and a controller which controls the movements of theconveyer and the movements and ejection volume of the pipette. Further,when a reaction cup having an open top covered with a tacky foil isused, a tacky foil breaker which breaks the tacky foil open is provided.

[0057] The storage means 2 stores test order information including theabove-mentioned sample identification information and specific componentinformation which identifies at least one specific component in a sampleto be measured, in the embodiment in the Figure, the test orderinformation 1 includes sample identification information on eightsamples expressed by combinations of English letters and numerals(S.ID01, . . . , S.ID08) and specific component information expressed byEnglish letters (FER, AFP and the like) indicating the specificcomponents in each component to be measured. The test order informationmay include personal information on examinees (such as names, birthdaysand gender) and the name of the medical institute in addition to sampleidentification information and specific component information.

[0058] The storage means 2 includes an input device as an interfacewhich inputs sample identification information and specific componentinformation. When a computer in utilized to construct the storage means,a keyboard or a touch panel is connected to the computer to be used asan input device. When a computer in utilized to construct the storagemeans, the computer may be segregated from the main body of theautomatic analyzer of the present invention. As an external computerlike this, a host computer for total management of test information at amedical institute may be used.

[0059] The first identification means reads the sample identificationinformation on a sample cup and sends the information into the work listpreparing means. There is no particular restriction on the firstidentification means, and for example, it may be a bar code reader whenthe sample identification information is expressed by a bar code, anoptical reader such as a small scanner and a video recorder when thesample identification information is expressed by letters or symbols, ora magnetic reader when the sample identification information is recordedin a magnetic recording medium. The first identification means may be ahandy means connected to the automatic analyzer of the present inventionor may be constructed by a sample cup carrier provided in a certainplace on the analyzer and a means which identifies a sample cup.

[0060] The work list preparing means 6 receives the sampleidentification information read by the first identification means 5,extracts the specific component information on the specific component(s)measured for the sample and prepares a work list including the specificcomponent information indicating the specific component(s) in the sampleto be measured. The work list preparing means 6 may includes a displayor output device to display or output the resulting work list.

[0061] The loading order determination means determines the order inwhich the operator should load sample cups and reaction cups on thecommon conveyer on the basis of the work list. The loading orderdetermination means gives instructions about the loading order bydisplaying the loading order on a display device or outputs the loadingorder from an output device. The loading order determination means maybe omitted if the work list preparing means has the same functions. InFIG. 3, the work list preparing means functions as a loading orderdetermination means as well and not only prepares a work list but onlydisplays the loading order of sample cups and reaction cups on thedisplay 7.

[0062] The loading order determination means may determine the order inwhich sample cups and reaction cups are loaded on the conveyer accordingto only the order of the sample identification information read by thefirst identification means reads, but preferably it should calculate theorder of samples which leads to the most efficient analysis from all thesample identification information ever read and the specific componentinformation extracted from the storage means based on the sampleidentification information and determine the order in which sample cupsand reaction cups are loaded on the conveyer. For example, the loadingorder determination means may be a computer so programmed as to appointreaction cups used for specific components which require dilution of thesample before determination to the end of the loading order of thesample cup containing the sample and the reaction cups used fordetermination of the specific components in the sample, or appoint thecups used for specific components which do not require dilution ofsamples to the top of the loading order of cups used for severalsamples.

[0063] The loading order of the reaction cups only among all the cups ofwhich loading order is determined by the loading order determinationmeans, namely the order of the specific components to be measured, ispreferably output into a controller which controls the automaticanalyzer in whole. This way, the operator does not have to do more thanload sample cups and reaction cups on the conveyer by following theinstruction on the loading order from the loading order determinationmeans, and the analyzer automatically does measurements and outputs theresults. Of course, the controller may control the pipette or the likebased on the output from another means which identifies specificcomponent information presented on reaction cups or from a thirdidentification means which will be described later.

[0064] Once the cups are loaded on the conveyer in the order determinedby the loading order determination means, and the measurements arestarted, the loaded cups are carried to the respective units asmentioned above in the analyzer by the conveyer. To the automaticanalyzer of the present invention, a second identification means 8 isprovided near the track of the conveyer to read at least the specificcomponent information presented on reaction cups on the moving conveyerand send it to a collating means 12. The collating means 12 compares thespecific component information read by the second identification meanswith the order determined by the loading order determination means andindicates or outputs whether or not they are matched on a display orfrom an output device.

[0065] There is no particular restriction on the second identificationmeans, and for example, it may be a bar code reader when the sampleidentification information is expressed by a bar code, an optical readersuch as a small scanner and a video recorder when the sampleidentification information is expressed by letters or symbols, or amagnetic reader when the sample identification information is recordedin a magnetic recording medium. Because the second identification meansreads specific component information on reaction cups on the movingconveyed, specific component information should be so located onreaction cups so that the second identification means can read it, forexample, on the tacky foil covering the open top of a reaction cup, asshown in FIG. 4. When a reaction cup having an open top covered with atacky foil is used, the second identification means should be providedahead of the tacky foil breaker because the tacky foil has to be brokenprior to measurement.

[0066] In the present invention, in addition to the secondidentification means, a third identification means 9 is preferablyprovided near the track of the conveyer to automatically read the sampleidentification information on sample cups conveyed by the conveyersequentially. The sample identification information thus read is sent tothe collating means 12 sequentially and compared with the loading orderof sample cups and reaction cups determined by the loading orderdetermination means and indicates or outputs whether or not they arematched on a display or from an output device.

[0067] The collating means 12 may command the controller to stop themeasurement, for example, as well as indicates or outputs that the orderof reaction cups determined by the loading order determination means andthe output from the second identification means are not matched on adisplay or from an output device, if they are not matched.

[0068] For example, if the sample identification information and/or thespecific component information includes information which makes themdistinguishable, the functions of the second identification means andthird identification means can be combined by one identification means.In such a case, the sample identification information on sample cups andthe specific component information on reaction cups have to be adjustedat about the same position. However, because sample cups and reactioncups are usually different in shape and size, it is usually difficult toread sample identification information and specific componentinformation by one means. In this case, it is preferred to provide athird identification means in addition to the second identificationmeans. The two identification means preferably read respectiveinformation from different directions, for example, sampleidentification information presented on the lateral side of a sample cupand specific component information presented on the open top of areaction cup, to avoid mixing up the information read by them.

[0069] The automatic analyzer of the present invention having theabove-mentioned structure can detect operational errors by man whichhappen when sample cups and/or reaction cups are loaded on the conveyer.

[0070] Particularly, cups are preferably loaded on a restricted part ofthe conveyer so that cups are not loaded on or off downstream from wherethe second identification means or the third identification means readinformation.

[0071] Now, the automatic analyzer shown in FIG. 3 will be explainedfrom the viewpoint of an operator of the analyzer. The operator exposesa sample cup 3 containing samples to be examined, for example, withsample identification information such as S.ID01 given as a bar codesstuck on it, to a bar code reader as the first identification means 5,and the first identification means 5 reads the sample identificationinformation and sends it to the work list preparing means 6.

[0072] The work list preparing means 6 extracts the specific componentinformation (FER) about the specific component to be measured for thesample assigned to the sample identification information S.ID01 from thetest order information stored in the storage means 2 and prepares a worklist including the sample identification information (S.ID01) an thespecific component information (FER). When the storage device is anexternal computer system, the specific component information relatingthe sample identification information is communicated between theautomatic analyzer and the external computer through an externalcommunication means for preparation of the work list

[0073] In this embodiment, the work list preparing means functions as aloading order determination means too and gives instructions to theoperator about the loading order of cups, in this case instructions toload the sample cup carrying the sample identification informationS.ID01 first and then a reaction cup carrying specific componentinformation FER, on a display device. The operator places the sample cupcarrying the sample identification information S.ID01 at the frontposition A on the conveyer 10 and then a reaction cup for measurement ofFER at the position B behind it, as instructed.

[0074] The operator exposes the sample cup 3 containing the next sampleto be examined, for example, with sample identification information suchas S.ID05 given as a bar codes stuck on it, to the first identificationmeans 5 in the same manner as described above, to have the sampleidentification information read, and the specific component informationTSH and FT4 corresponding to the sample identification informationS.ID05 are added to the specific component information FER correspondingto the sample identification information S.ID01 in the work list, on thedisplay device 7 as shown in FIG. 3. The operator places the sample cupcarrying the sample identification information S.ID05 at the position Con the conveyer 10, then a reaction cup for measurement of TSH at theposition D and a reaction cup for measurement of FT4 at the position E.

[0075] The analyzer of the present invention conveys sample cups andreaction cups intermixedly by a single conveyer and therefore can besimplified structurally as compared with those which convey sample cupsand reaction cups by two conveyers separately and is easily available insmall size. Further, because it dispenses with a conveyer as one movingpart, it requires less frequent maintenance and can be produced at alower cost. Further, because the conveyer which conveys reaction cups ona closed track does not have to be stopped when a new sample to beanalyzed and reaction cups necessary for its analysis are loaded on theconveyer instead of the previous sample which has been already analyzed,the analyzer of the present invention can perform efficient analyses.

[0076] Because the reactor is provided separately from the conveyer toadjust reaction cups at a predetermined temperature for the reaction andserve as the detection site as well, and reaction cups are carriedbetween the conveyer and the reactor by the reaction cup lift whichreciprocates straight, the reactor and the conveyer in the analyzer ofthe present invention can have simple structures. Because the trashbinwhich collects used reaction cups is provided on the straight track ofthe reaction cup lift, the reaction cup lift is only required toreciprocate on the straight track and move up and down above thestraight track and requires just a simply drive unit.

[0077] Because the nozzle unit which sucks in and out samples fromsample cups is only required to reciprocate on a straight track and moveup and down at arbitrary points like the reaction cup lift, the nozzleunit requires only a simple drive unit. Besides, because the straighttrack of the nozzle unit is covered by (identical to or part of) thestraight track of the reaction cup lift, the analyzer can be simplifiedby combining the drive units for reciprocation of them on these straighttracks.

[0078] Because in the analyzer of the present invention, the closedtrack of the conveyer necessarily has a straight part which accommodatesat least two cups and is overlapped by the straight tracks of the nozzleunit and the reaction cup lift so that the nozzle unit and the reactioncup lift reciprocate over the straight part, once the cups required foran analysis are carried to the straight part, the rest of the analysiscan be done by moving the nozzle unit and the reaction cup lift back andforth and up and down without moving the conveyer though it depends onthe capacity of the straight part.

[0079] Thus, the analyzer according the first aspect of the presentinvention do not require quicker and more frequent motions of theconveyer to do an analysis in a shorter time with improved efficiency,additional sample cups or reaction cups can be easily loaded on theconveyer. Therefore, the analyzer of the present invention can cope withanalysis of a large number of samples by loading additional sample cupsand reaction cups one after another without increasing the size of theconveyer. Use of the analyzer of the present invention for clinicaldiagnoses from the necessity of immediate analyses facilitatesreplacements of sample cups and reaction cups and enables cut-inanalyses of urgent samples.

[0080] The automatic analyzer according to the second aspect of thepresent invention which adopts the means (1) to (6) can remove thepossibility of diagnostic errors based on the measured values ofspecific components obtained when the operator has loaded sample cupsand reaction cups on the conveyer in the wrong order or used the wrongreaction cups.

[0081] By virtue of the storage means, the automatic analyzer of thepresent invention can check the sample identification information readby the first identification means for read errors. By virtue of thefirst identification means, the automatic analyzer of the presentinvention does not require the operator to visually read the sampleidentification information presented on sample cups or input theinformation through an input device such as an keyboard and thereforecan not only remove read and input errors by the operator but alsolighten the operator's work. The work list preparing means and theloading order determination means enable the automatic analyzer of thepresent invention to lessen the possibility that the operator loadssample cups and reaction cups on the conveyer in the wrong order.

[0082] By virtue of the second identification means, and, if present,the third identification means which is preferably provided, theautomatic analyzer of the present invention can indicate loading errorsmade by loading of sample cups or reaction cups in the wrong order bythe operator and stop the analysis.

1. An analyzer which determines a specific component in a sample whileconveying a sample cup containing the sample and a reaction cupcontaining a reagent which reacts with the sample, which ischaracterized in that: (1) the analyzer comprises a conveyer whichconveys sample cups and reaction cups intermixedly on a closed track,(2) the analyzer comprises a reactor which is equipped with a thermostatwhich maintains the reaction cups at a predetermined temperature, atrashbin which collects used reaction cups, an up-down nozzle unit whichsucks in and out a predetermined amount of a sample and a reaction cuplift which carries a reaction cup between the conveyer, the reactor andthe trashbin, (3) the nozzle unit and the reaction cup lift reciprocateon a straight track, driven by different drive units separately or bythe same drive unit, (4) the trashbin is placed on the straight track ofthe reaction cup lift, (5) at least part of the closed track of theconveyer is straight and overlaps the straight track of the nozzle unitand the reaction cup lift, and (6) the straight part of the track of theconveyer accommodates at least two cups.
 2. The analyzer according toclaim 1, wherein the nozzle unit and the reaction cup lift are mountedon the same pedestal that reciprocates on the straight track, driven bythe same drive unit.
 3. The analyzer according to claim 1, whichcomprises a reagent conveyer which conveys a reagent reservoircontaining a reagent on a straight track crossing the straight track ofthe nozzle unit.
 4. The analyzer according to claim 1, which comprises atip conveyer which carries a tip to be put on the nozzle means on atrack crossing the straight track of the nozzle unit.
 5. The analyzeraccording to claim 1, which comprises a detector which detect acomponent in a reaction cup in the reactor.
 6. The analyzer according toclaim 1, which comprises a reaction cup washer which washes reactioncups in the reactor.
 7. The analyzer according to claim 1, whichanalyzes a sample by using a reaction cup prepacking a reagentappropriate for a specific component in the sample to be analyzed.
 8. Anautomatic analyzer which determines a specific component in a samplewhile intermixedly conveying a sample cup containing the sample whichpresent sample identification information which identifies the sample inthe sample cup and a reaction cup containing a reagent for determinationof the specific component in the sample which presents specificcomponent information which identifies the specific component by oneconveyer, wherein the automatic analyzer comprises: (1) a storage meanswhich stores test order information including specific componentinformation to identify at least one specific component to be measuredfor each sample, (2) a first identification means which reads the sampleidentification information presented by each sample cup, (3) a work listpreparing means which selects the specific component information whichidentifies at least one specific component in the sample to be measuredfrom the test order information stored in the storage means on the basisof the sample identification information for the sample read by thefirst identification means and prepares a work list consisting of thesample identification information for sample and the specific componentinformation identifying the specific component(s) in the sample to bemeasured, (4) a loading order determination means which determines theorder in which sample cups and reaction cups are loaded on the singleconveyer from the work list, (5) a second identification means whichautomatically reads the specific component information presented by areaction cup conveyed by the conveyer, and (6) a collating means whichcompares the specific component information read by the secondidentification means with the determined order and indicates whether ornot they are matched.
 9. The automatic analyzer according to claim 8,wherein the sample identification information presented on a sample cupbeing conveyed by the conveyer is automatically read by the secondidentification means or a third identification means, and the collatingmeans compares the specific component information and the sampleidentification information with the work list.